Archive for the ‘Cloning’ Category

In our long stride toward the inevitable designer babies, the first manipulation has been the noble goal of creating babies free of the mitochondrial diseases carried by their mothers. This series will examine the issue rather thoroughly in four basic segments:

1. The basic cell biology involved.
2. The problem of defective mitochondria.
3. The technique involving three-parent embryo creation.
4. The current state of the ethics debate among governmental bodies here and in the United Kingdom.

Cell Biology

In order to understand the fullness of the debate, we need to understand some very basic facts about cells. Every human cell contains specialized compartments called Organelles (meaning, Little Organs). Just as the human body has organs for specialized function (heart, lungs, stomach, intestines, brain, liver, kidneys, etc.) so too every cell has little organs for specialized function:

Ribosomes make protein.Nucleus houses the Chromosomal DNA.Lysosomes do recycling of worn out parts.Golgi Bodies modify and ship proteins to appropriate destinationsEndoplasmic Reticula make lipids and are sites of protein synthesis.

and then come the Mitochondria.

The mitochondria are frequently referred to as the powerhouse of the cell, because they take in by-products of glucose and extract large amounts of energy for use by the cell. It takes a great deal of energy for cells to function properly, and the mitochondrion is the place where that happens. That having been said, it is one of the gross oversimplifications in biological education to leave it at energy production and move on where the mitochondrion is concerned. In fact, there are two scientific journals devoted entirely to mitochondrial research that immediately come to mind: Mitochondrion, and Mitochondrial Research. Suffice it to say that the scope of the mitochondrion and its effects on human physiology are broad and complicated.

For purposes of understanding three-parent embryo creation it helps to know the following. It is thought in evolutionary biology that at one time the mitochondrion was a free-standing, free-living cell that became incorporated into larger cells, with the result being a marriage that worked for both. It’s called the Endosymbiont Theory. Mitochondria replicate themselves within cells, so when cells divide, each new cell gets an appropriate number of mitochondria. In this way, the mitochondria act somewhat as independent organisms would. Along the way, most of the mitochondrion’s 3,000 genes ended up being transferred to the cell nucleus. The following description comes from the United Mitochondrial Disease Foundation website. I have found them to be an excellent clearinghouse of information with writing that is very easy for the scientific layperson to follow:

The conventional teaching in biology and medicine is that mitochondria function only as “energy factories” for the cell. This over-simplification is a mistake which has slowed our progress toward understanding the biology underlying mitochondrial disease. It takes about 3000 genes to make a mitochondrion. Mitochondrial DNA encodes just 37 of these genes; the remaining genes are encoded in the cell nucleus and the resultant proteins are transported to the mitochondria. Only about 3% of the genes necessary to make a mitochondrion (100 of the 3000) are allocated for making ATP. More than 95% (2900 of 3000) are involved with other functions tied to the specialized duties of the differentiated cell in which it resides. These duties change as we develop from embryo to adult, and our tissues grow, mature, and adapt to the postnatal environment. These other, non-ATP-related functions are intimately involved with most of the major metabolic pathways used by a cell to build, break down, and recycle its molecular building blocks. Cells cannot even make the RNA and DNA they need to grow and function without mitochondria. The building blocks of RNA and DNA are purines and pyrimidines. Mitochondria contain the rate-limiting enzymes for pyrimidine biosynthesis (dihydroorotate dehydrogenase) and heme synthesis (d-amino levulinic acid synthetase) required to make hemoglobin [Note by G.N.: This is the molecule that binds oxygen in every red blood cell]. In the liver, mitochondria are specialized to detoxify ammonia in the urea cycle. Mitochondria are also required for cholesterol metabolism, for estrogen and testosterone synthesis, for neurotransmitter metabolism, and for free radical production and detoxification. They do all this in addition to breaking down (oxidizing) the fat, protein, and carbohydrates we eat and drink.

Do visit their website for specific information on the range of mitochondrial diseases.

Now, without frightening off the non-scientist or non-medical person, the above quote cracks the door ajar ever so slightly to allow a glimpse of the complexities involved at the biological level. Adding further, there needs to be coordination between the genes encoded on mitochondrial DNA (mtDNA) and the mitochondrial genes encoded on the DNA in the nucleus of the cell (nDNA). To date, there are still too many unknowns in the cell biology and the pathophysiology at the cellular level (That’s why the journals devoted to mitochondrial research are going strong, and will be for years to come.). We don’t know all of the coordinated function between mtDNA and nDNA within a given individual, and what other factors there may be (as yet unknown) that govern such function. In other words, are all mitochondrial defects solely attributable to mitochondrial genes (mt DNA and nDNA), or are there other genetic/biochemical defects in the individual at play here? It matters when someone wishes to take the mitochondria from an egg cell, leaving the nDNA intact, and introducing mitochondria from another individual. It matters because the issues are not always so simple as mutations in genes.

Indeed there are other factors around the major genetic factors, and these are known as epigenetic factors. Epigenetics looks at factors involved in the regulation of genes, and when they get turned on and off. Adding still further to the complexity, there may be epigenetic factors in the nDNA that are unknown and alter the epigenetics of the mtDNA., and all of these factors in one kind of cell may well influence mitochondrial function in distant types of cells within the body.

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Note: There seems to be two different protocols that have been reported on this, as Melissa points out in the combox below. I’ll track down the correct one and adjust accordingly.

News today from AP that a research team at Oregon Health and Sciences University has replicated work done a few years ago in Britain, constructing a human embryo by using the eggs of two mothers and a father’s sperm.

The goal here is to prevent diseases that arise from genetic defects within the energy-producing organelle of the cell known as the mitochondrion. These so-called mitochondrial diseases are very real and quite varied. As the article states:

About 1 in every 5,000 children inherits a disease caused by defective mitochondrial genes. The defects can cause many rare diseases with a host of symptoms, including strokes, epilepsy, dementia, blindness, deafness, kidney failure and heart disease.

So the diseases and the frequencies are significant. The ethics are a forgone conclusion. We’ll debate the ethics of taking the healthy nucleus from Jane’s egg and putting it into the egg of Lisa (which has had its nucleus removed), and then fertilizing that hybrid with Jane’s husband’s sperm. In this way, they will have children with 99% DNA from Jane and hubby, and only 1% DNA residing in the mitochondrion.

What effect will this have on the offspring, and will there be complications? We won’t know until we manufacture these babies and await the results not only over the course of the manufactured baby’s life, but in the lives of the descendants.

It won’t stop there.

The next step will be the genetic engineering of nuclear DNA by either replacing entire chromosomes, or at the least, defective nuclear genes. The guiding ethical principle?

Suffering is bad, and the noble end of preventing suffering justifies the means.

Emanating from this nobility comes the evil of intolerance of those who suffer, and who afflict us with their suffering. Consider the following from U.S. Supreme Court Justice Oliver Wendell Holmes, Jr. in his infamous majority opinion in the 1927 Buck v. Bell case which upheld the forced sterilization of the developmentally delayed:

Carrie Buck is a feeble minded white woman who was committed to the State Colony above mentioned in due form. She is the daughter of a feeble minded mother in the same institution, and the mother of an illegitimate feeble minded child…

An Act of Virginia, approved March 20, 1924, recites that the health of the patient and the welfare of society may be promoted in certain cases by the sterilization of mental defectives, under careful safeguard, &c.; that the sterilization may be effected in males by vasectomy and in females by salpingectomy, without serious pain or substantial danger to life; that the Commonwealth is supporting in various institutions many defective persons who, if now discharged, would become [p206] a menace, but, if incapable of procreating, might be discharged with safety and become self-supporting with benefit to themselves and to society…

We have seen more than once that the public welfare may call upon the best citizens for their lives. It would be strange if it could not call upon those who already sap the strength of the State for these lesser sacrifices, often not felt to be such by those concerned, in order to prevent our being swamped with incompetence. It is better for all the world if, instead of waiting to execute degenerate offspring for crime or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind. The principle that sustains compulsory vaccination is broad enough to cover cutting the Fallopian tubes. Three generations of imbeciles are enough.

There’s nothing new in our age.

When suffering is to be avoided at all costs, the question becomes, “WHOSE suffering?”

The answer to that question then determines the lengths to which we will go to prevent that suffering.

The next step will be designer babies, and on what grounds could parents possibly be stopped? That it’s unethical to manufacture human beings in a lab? Are they humans in that Petri dish? If yes, why do we discard so many during normal IVF? Is that not murder? If the answer is no, then what harm is there? Isn’t genetic engineering for traits just a cleaner and more precise version of picking up a blonde-haired, blue-eyed stud in a bar, or picking out an Ivy-League sperm donor?

Abortion and abortion’s apologists have succeeded in twisting and distorting even a once-objective, just-the-facts, and statistically-oriented discipline as Public Health. In the not-so distant past, pregnancy was defined in medical textbooks as the result of fertilization of egg by sperm. Now it’s defined as implantation of the embryo in the uterus. Semantics? Hardly.

This represents a fundamental shift that protects the in vitro fertilization industry. If pregnancy is defined by implantation, then there is hardly an ethical hurdle when it comes to sifting through dozens of embryo’s in search of the ‘most fit’. Some might call them ‘keepers’. The rest may simply be discarded.

The in vitro fertilization industry and its related embryonic stem cell research industry, which makes use of ‘leftover’ embryos in frozen storage, serve as a bulwark for abortion, appealing to utilitarian sentiments regarding the alleviation of emotional and physical suffering, respectively.

Even defining something as simple as infant mortality has become a semantic three-ring circus.

A look at figure #1 in the study doesn’t inspire confidence as the study bills itself as a comparison between the U.S. and Europe, but goes on to include Singapore, Hong Kong, Japan, Israel, Australia, New Zealand, Canada, and Cuba.

Table #1 inspires even less confidence as it details what constitutes ‘live births’ in the countries under study. The following countries take the most expansive definition of ‘live birth’ to include any birth of a living baby without regard to gestational age:

Norway, Czech Republic, France, Ireland, Netherlands, Poland are listed as having varying reporting criteria, including a 500 gram birthweight, gestational age, and in the Czech Republic, the added requirement that the infant survives the first 24 hours.

No mention at all of the remaining 12 countries in the study.

Additionally, the study claims, “Differences in national birth registration notwithstanding, there can also be individual differences between physicians or hospitals in the reporting of births for very small infants who die soon after birth.”

It’s difficult to compare nations to one another when the very definition of ‘live birth’ is up for grabs, when different nations take a more or less aggressive approach to saving the life of the neonate.

These approaches also have much top do with who is paying the bill. Governments with socialized medicine and flat economies have a powerful disincentive to attempt aggressive, costly life-saving measures, and may well be more apt to recommend abortion in cases where fetal anomalies are detected, further skewing the data.

LifeNews.com reports on 12/1/09 that President Obama, who had terminated the President’s Council on Bioethics three months before it was set for its September term limit, has constituted a new Council that may be more ideologically aligned with himself. If so, this could mean an opening into human cloning.

To be fair, Presidents reserve the right to constitute the Councils as they see fit. That said, President George W. Bush created his Council with a 50/50 ideological split. We’ll see what Obama does.

Don’t look for cloning by name. Look for legislation that funds “somatic cell nuclear transfer technology”, which is cloning’s technical name. If we can support embryo-destructive research in the pursuit of therapeutics, we’ll support cloning to achieve the same end.